TY - JOUR
T1 - A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts
AU - Dullaers, Melissa
AU - Li, Dapeng
AU - Xue, Yaming
AU - Ni, Ling
AU - Gayet, Ingrid
AU - Morita, Rimpei
AU - Ueno, Hideki
AU - Palucka, Karolina Anna
AU - Banchereau, Jacques
AU - Oh, Sang Kon
N1 - Funding Information:
We thank E. Kowalski and S. Coquery in the FACS Core at BIIR and D. Su in the Tissue Bank at Baylor hospital. We thank W. Leonard (NIH) and J. Skinner (BIIR) for critical reading of this manuscript. We also thank M. Ramsay and W. Duncan for supporting this study. This study was supported by a pilot project (S.O.) in U19 AI057234 (J.B.) and BHCS Foundation (S.O. and J.B.). M.D., J.B., and S.O. designed experiments and wrote the manuscript. M.D. performed experiments. Y.X. and I.G. helped with experiments. D.L., L.N., and R.M. provided technical advice. H.U., K.A.P., J.B., and S.O. provided technical advice and conceptual guidance.
PY - 2009/1/16
Y1 - 2009/1/16
N2 - Mucosal immunoglobulin A (IgA) secreted by local plasma cells (PCs) is a critical component of mucosal immunity. Although IgA class switching can occur at mucosal sites, high-affinity PCs are optimally generated in germinal centers (GCs) in a T cell-dependent fashion. However, how CD4+ helper T cells induce mucosal-homing IgA-PCs remains unclear. Here, we show that transforming growth factor β1 (TGFβ1) and interleukin 21 (IL-21), produced by follicular helper T cells (Tfh), synergized to generate abundant IgA-plasmablasts (PBs). In the presence of IL-21, TGFβ1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGFβ1 and IL-21 downregulated CXCR5 while upregulating CCR10 on plasmablasts, enabling their exit from GCs and migration toward local mucosa. This was supported by the presence of CCR10+IgA+PBs in tonsil GCs. These findings show that Tfh contribute to mucosal IgA. Thus, mucosal vaccines should aim to induce robust Tfh responses.
AB - Mucosal immunoglobulin A (IgA) secreted by local plasma cells (PCs) is a critical component of mucosal immunity. Although IgA class switching can occur at mucosal sites, high-affinity PCs are optimally generated in germinal centers (GCs) in a T cell-dependent fashion. However, how CD4+ helper T cells induce mucosal-homing IgA-PCs remains unclear. Here, we show that transforming growth factor β1 (TGFβ1) and interleukin 21 (IL-21), produced by follicular helper T cells (Tfh), synergized to generate abundant IgA-plasmablasts (PBs). In the presence of IL-21, TGFβ1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGFβ1 and IL-21 downregulated CXCR5 while upregulating CCR10 on plasmablasts, enabling their exit from GCs and migration toward local mucosa. This was supported by the presence of CCR10+IgA+PBs in tonsil GCs. These findings show that Tfh contribute to mucosal IgA. Thus, mucosal vaccines should aim to induce robust Tfh responses.
KW - CELLIMM
UR - http://www.scopus.com/inward/record.url?scp=58149242530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149242530&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2008.11.008
DO - 10.1016/j.immuni.2008.11.008
M3 - Article
C2 - 19144318
AN - SCOPUS:58149242530
SN - 1074-7613
VL - 30
SP - 120
EP - 129
JO - Immunity
JF - Immunity
IS - 1
ER -